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COVID-19 Incidence and Death Rates Among Unvaccinated ...
This report describes higher protection against COVID-19 infection and death among people who received an updated booster than people who received a monovalent booster.
www.cdc.gov
COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination — 24 U.S. Jurisdictions, October 3, 2021–December 24, 2022
Summary
What is already known about this topic?COVID-19 vaccine effectiveness decreased with waning of vaccine-derived immunity and emerging Omicron sublineages. An updated (bivalent) booster dose enhances protection against infection and medically attended illness, but protection against death has not been evaluated.
What is added by this report?
Bivalent booster recipients in 24 U.S. jurisdictions had slightly higher protection against infection and significantly higher protection against death than was observed for monovalent booster recipients or unvaccinated persons, especially among older adults.
What are the implications for public health practice?
Bivalent COVID-19 booster doses protected against infection and death during BA.4/BA.5 circulation. All eligible persons should get 1 bivalent booster dose ≥2 months after their COVID-19 primary series or last monovalent booster dose.
On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).* To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5) predominance.† During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65–79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65–79 years; 8.3 and ≥80 years; 4.2). In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in relative COVID-19 mortality rates among unvaccinated persons compared with persons receiving who had received a monovalent booster within 2 weeks–2 months. During the early BA.4/BA.5 period, declines in relative mortality rates were observed at 6–8 (RR = 4.6), 9–11 (4.5), and ≥12 (2.5) months after receiving a monovalent booster. In contrast, bivalent boosters received during the preceding 2 weeks–2 months improved protection against death (RR = 15.2) during the late BA.4/BA.5 period. In both analyses, when compared with unvaccinated persons, persons who had received bivalent boosters were provided additional protection against death over monovalent doses or monovalent boosters. Restored protection was highest in older adults. All persons should stay up to date with COVID-19 vaccination, including receipt of a bivalent booster by eligible persons, to reduce the risk for severe COVID-19.
Previous reports on COVID-19 vaccine impact indicated that protection against infection and, to a lesser degree, severe illness, declined with waning of vaccine-induced immunity and emergence of the SARS-CoV-2 Delta and Omicron variants§ (1–4). After Omicron (BA.1) became predominant in the United States in late December 2021, Omicron sublineages BA.2, BA.4, and BA.5 circulated at high prevalence; BA.4 and BA.5-related variants constituted 78% of circulating lineages by December 24, 2022. Food and Drug Administration (FDA)–authorized bivalent boosters, which include an additional Omicron BA.4/BA.5 spike component, have been shown to enhance protection against infection and medically attended illness (5–7).
Weekly counts of COVID-19 cases (October 3, 2021–December 24, 2022) and associated deaths (October 3, 2021–December 3, 2022) by primary series vaccination and booster status, including bivalent boosters (the week starting September 18, 2022), were reported from 24 jurisdictions¶ that routinely link case surveillance data to immunization registries (vaccinations) and vital registration databases (deaths). Accounting for case and death reporting lags (2 weeks and 5 weeks, respectively) permitted more complete reporting, data linkage, and mortality ascertainment. Standardized definitions were used for COVID-19 cases** and COVID-19–associated deaths†† by vaccination status§§ with specimen collection dates used as reference dates; vaccinated persons who did not complete a primary COVID-19 vaccination series were excluded. Analysis periods were determined based on U.S. variant proportion estimates. Rate denominators were calculated from vaccine administration data, with numbers of unvaccinated persons estimated by subtracting numbers of persons vaccinated with at least a primary series and persons with an incomplete primary series from 2019 U.S. intercensal population estimates.¶¶ A continuity correction assumed that ≥5% of each age group and jurisdiction would always be unvaccinated (i.e., ≤95% vaccination coverage).*** Average weekly incidence and mortality were calculated during each period and stratified by age group (12–17, 18–49, 50–64, 65–79 and ≥80 years) and vaccination status; overall rates were age-standardized using the 2000 U.S. Census Bureau standard population.††† Two sets of analyses of incidence and mortality rates overall (24 jurisdictions) and by time since last monovalent or bivalent booster vaccination (23 jurisdictions) were conducted. Overall and strata-specific RRs were calculated by dividing rates among unvaccinated persons by rates among vaccinated persons; after detrending the underlying linear changes in rates, 95% CIs were calculated from the remaining variation in observed weekly rates§§§ (8,9). SAS (version 9.4; SAS Institute) and R (version 4.1.2; R Foundation) were used to conduct all analyses. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¶¶¶
Among persons aged ≥12 years, a total of 21,296,326 COVID-19 cases and 115,078 associated deaths were reported during October 3, 2021–December 24, 2022, and October 3, 2021–December 3, 2022, respectively, from 24 U.S. jurisdictions (Table). Average weekly age-standardized incidence and mortality (cases and deaths per 100,000 population aged ≥12 years) increased substantially during the Omicron BA.1 period and to a lesser extent during the early BA.4/BA.5 period (Figure 1). During all periods, average weekly age-standardized incidence and mortality were consistently higher among unvaccinated persons (ranges = 216.1–1,256.0 and 1.6–15.8, respectively) than among monovalent-only vaccine recipients (ranges = 86.4–487.7 and 0.3–1.4, respectively); average weekly incidence and mortality during the late BA.4/BA.5 period were lowest among bivalent booster recipients (78.5 and 0.1, respectively).
Overall, age-standardized case RRs (unvaccinated persons compared with monovalent-only vaccine recipients) declined from 4.0 during the Delta period to 2.6 during the Omicron BA.1 and 1.8 during the Omicron BA.2 periods, before increasing to 2.7 in the early BA.4/BA.5 period. Overall case RRs (unvaccinated persons compared with bivalent booster recipients) were slightly higher (2.8) than were those for monovalent-only vaccine recipients (2.5) during the late BA.4/BA.5 period. Average, age-standardized mortality RRs in monovalent-only vaccine recipients decreased from the Delta (16.2) to BA.1 (11.5) period, then stabilized during the BA.2 (5.3), early BA.4/BA.5 (5.3), and late BA.4/BA.5 (5.4) periods. Overall mortality rates among unvaccinated persons were 14.1 times the rates among bivalent vaccine recipients; mortality rates among monovalent-only vaccine recipients were 2.6 times the rates among bivalent vaccine recipients during the late BA.4/BA.5 period. Compared with unvaccinated persons, protection among bivalent booster recipients aged 65–79 years (RR = 23.7), and ≥80 years (10.3) was significantly higher than was protection among monovalent booster recipients aged 65–79 years (8.3) and ≥80 years (4.2).
In stratified comparisons of unvaccinated persons and vaccinated persons who had received a monovalent booster dose 2 weeks–2 months earlier, progressive declines in case RRs were more pronounced between the Delta (7.0) and BA.1 (3.4), BA.2 (2.4), early BA.4/BA.5 (2.8), and late BA.4/BA.5 (2.8) periods; the case RR at 2 weeks–2 months after a bivalent booster (2.8) was the same during the late BA.4/BA.5 period (Figure 2) (Supplementary Table, https://stacks.cdc.gov/view/cdc/124201).**** A similar reduction in the case RR was observed for both the monovalent booster at 3–5 months (2.0) and the bivalent booster at 3 months (1.7) after vaccination during the late BA.4/BA.5 period. Mortality RRs for unvaccinated persons compared with persons who received a monovalent booster dose 2 weeks–2 months earlier declined from 50.7 during the Delta period to 21.4 during the BA.1 period, 7.9 during the BA.2 period, and 7.4 during the early BA.4/BA.5 period, representing a reduction in crude vaccine effectiveness (VE) from 98% (Delta) to 87% (BA.4/BA.5).†††† During the early BA.4/BA.5 period, mortality RRs remained stable 3–5 months after receiving a monovalent booster dose (7.2) but declined to 4.6 at 6–8 months, 4.5 at 9–11 months, and 2.5 at ≥12 months. In contrast, bivalent boosters received in the preceding 2 weeks–2 months during the late BA.4/BA.5 period provided enhanced protection against death (mortality RR = 15.2 in unvaccinated persons versus bivalent booster recipients), representing a crude VE of 93%. A subset analysis of the Omicron BA.5, BA.4, and BA.2-related variant period (November 6–December 24, 2022) yielded similar results.
